Mammalian blood vessels are composed of three layers: the adventitia, media and intima, and the intima is covered with a layer of vascular endothelial cells. The vascular endothelial cells release various types of vasoactive substances to control the contraction and expansion of blood vessels, and also protect blood vessels by preventing the adhesion and aggregation of platelets.
Examples of diseases in which vascular endothelial cells are involved include arteriosclerosis that begins with a decrease in the function of endothelial cells present in vascular intima. Endothelial dysfunction, namely, the loss of endothelial function, induces vascular diseases, such as for example, atherosclerosis. Vascular endothelial cells and endothelial progenitor cells (EPCs) have been suggested to be useful for therapeutic applications, and cases have been reported in which a revascularization therapy of transplanting autologous EPCs to patients with severe ischemic diseases including coronary artery diseases and lower limb ischemic diseases (such as Buerger's disease, obstructive arteriosclerosis, etc.) was performed to obtain favorable results (Non-patent Documents 1 and 2). The above described effect of improving ischemia has been confirmed to be dependent on the number of EPCs administered, and thus it is important to obtain and administer a larger amount of EPCs. However, the number and the function of EPCs obtained from autologous blood or bone marrow fluid of the patients are often decreased, and in such cases, a sufficient therapeutic effect cannot be obtained.
On the other hand, cells with pluripotency have hitherto been reported, such as induced pluripotent stem cells (iPS cells) which can be obtained by introducing undifferentiated cell-specific genes into embryonic stem cells (ES cells) or somatic cells (Patent Documents 1 and 2). These cells are drawing attention as useful materials, since they can be grown indefinitely, and there is a possibility that vascular endothelial cells for use in transplantation therapy can be obtained by applying a differential stimulus to these cells.
So far, a method for inducing the differentiation of human embryonic stem cells into endothelial cells (Patent Document 3), and methods for inducing the differentiation of human pluripotent stem cells into mesodermal cells have been examined (Patent Document 4, Non-patent Document 3 and Non-patent Document 4). However, no method has been reported to date which allows the induction to highly functional vascular endothelial cells from pluripotent stem cells at a high efficiency.